Boosting Brain Chemical Could Reverse Down Syndrome

Boosting a neurotransmitter called norepinephrine in sufferers of Down Syndrome could help reverse the condition, which is the most common cause of mental retardation in children, a study showed Wednesday.

"If you intervene early enough, you will be able to help kids with Down Syndrome to collect and modulate information," said Ahmad Salehi, the lead author of the study, which was published in Science Translational Medicine.

"Theoretically, that could lead to an improvement in cognitive functions in these kids," he said.

Salehi was part of a team of scientists at Stanford University School of Medicine and the Lucile Packard Children's Hospital in California who used a precursor of norepinephrine to reverse learning deficits in mice with symptoms very close to those seen in humans with Down Syndrome.

The study was the first to look at treating Down Syndrome by targeting the norepinephrine system, Salehi told AFP.

The mice had three copies of a fragment of mouse chromosome 16, while Down Syndrome occurs when each cell in the body has three copies of chromosome 21, instead of the usual two.

Children with Down Syndrome, like the mice in the study, suffer from contextual learning and memory deficits.

Although Down Syndrome kids are not developmentally delayed at birth, they fall behind as they age and "struggle to use spatial and contextual information to form new memories, a function that depends on the hippocampus part of the brain," the study says.

"As a result, they have trouble with learning to navigate complex environments such as a new neighborhood or a shopping mall," it says.

Normally, as contextual memories are formed, hippocampal neurons receive norepinephrine from neurons in another part of the brain, the locus coeruleus.

But in the study of the mice with the Down Syndrome-like condition, the researchers noted that the locus coeruleus began to degenerate early on in the mice's lives.

When the locus coeruleus broke down, the mice failed at simple cognitive tests that required them to be aware of changes in their environment.

For example, they did not build nests when placed in an unknown cage, whereas normal mice typically do when placed in a new environment.

But when the mice were given norepinephrine precursors, which are converted in the brain into the key neurotransmitter and hormone, the problem was fixed.

"This study explains why contextual learning is compromised in Down Syndrome and suggests a new therapeutic strategy, because so far we have been targeting other systems for treating people with Down Syndrome," said Salehi.

"It shows that it's the strategy (of targeting the norepinephrinic system that works, not one drug," Salehi said.

"If you use a drug that converts into norepinephrine or a drug that mimics norepinephrine and binds to norepinephrine receptors, that has the same effect," he said.

Drugs that treat other neurological conditions such as depression and attention deficit-hyperactivity disorder (ADHD) also target the norepinephrine system.

And the norepinephrine precursor used in the Down Syndrome study is currently in clinical trials to treat fibromyalgia in humans, a chronic condition characterized by fatigue and widespread pain.

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